Impaired Bmp signaling in Foxl1+ telocyte influence the maintenance of the intestinal stem cell niche
Bibliographic record
Abstract
New components of the intestinal stem cell niche are constantly being discovered. Recently, the subepithelial Foxl1 + telocytes (TC Foxl1+ ) were found to play a key role in maintaining and regulating intestinal crypt homeostasis. TC Foxl1+ produce crucial niche components such as WNT2b, WNT5a and RSPO3 as well as the Bone Morphogenic Proteins (BMP) inhibitors Gremlin 1 and 2. Previous work in our laboratory showed that epithelial BMP signaling is involved in terminal differentiation and maturation of cells from the secretory lineage. Our recent work showed that the loss of mesenchymal BMP signaling leads to the development of a pathological microenvironment inducing colonic and gastric polyposis in older mice, drawing attention to the impact of a pathogenic microenvironment in polyposis. By genetic means, we propose to address how BMP signaling in TC Foxl1+ modulates the intestinal stem cell niche. Using the Cre/loxP system, we generated mice with a deletion of BmpR1a in all gastrointestinal subepithelial TC Foxl1+ . Histological analysis and terminal differentiation assessment were performed with cellular staining and immunofluorescence (H&E, Alcian Blue and Lysozyme). Niche components were analysed by RT‐qPCR from crypt epithelium or total ileal RNA extracts. H&E staining on 9 months‐old BmpR1a ΔFoxl1+ and control mice ileum demonstrated perturbed architecture in the BmpR1a ΔFoxl1+ such as fused and enlarged villi compared to control mice. Alcian Blue staining showed an increase of goblet cells in the mutant mice. Electron microscopy showed that Paneth cells from mutant mice have larger vesicles than controls. The RT‐qPCR analysis showed a decrease in WNT signaling targets in the crypts epithelium cells. Indeed, LGR5 is decreased by 50% and mTERT by 34% in the mutant mice, whereas the stem cell marker BMI1 is not modulated. Maturity of Paneth cells is impaired in the mutant mice as shown by a 41% decrease in SOX9 expression. This lack in Paneth cell maturity is also reflected by a 60% decrease in WNT3 expression in BmpR1a ΔFoxl1+ mice, an important stem cell niche factor. Secretory cell determination transcription factor ATOH1 is decreased by 35% in the mutant mice. Analysis from total ileal extract revealed a decrease of WNT2b, a key niche factor from the mesenchymal cells. Thus, our results show that altering Bmp signaling in subepithelial TC Foxl1+ modulates crucial niche factors influencing intestinal stem cells homeostasis and their subsequent determination. Support or Funding Information Canadian Institutes of Health Research‐Institute of Nutrition, Metabolism and Diabetes
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".